Regional alveolar hypoxia induces pulmonary vasoconstriction localized to the hypoxic area. In the dog, this response is diminished 67% by sympathectomy. The factors responsible for the persisting response have not been identified. Histamine and prostaglandin F2 are uninvestigated but potential mediators, both of which are known to occur in the lung in high concentration, to be released during hypoxia, and to induce pulmonary vasoconstriction. It is proposed to investigate the role of histamine and prostaglandin in mediating the hypoxic vasoconstrictor response. Bilateral cervical sympathectomy will be done and the residual hypoxic vasoconstrictor response assessed. Pharmacologic blockade of histamine with chlorpheniramine maleate or of prostaglandin with Indocin will be done and the residual hypoxic vasoconstrictor response reassessed. In addition, it is proposed to investigate the role of prostaglandin F2 gamma in the intact animal in the alveolar hypoxic response by inducing blockade of the prostaglandins with Indocin. In addition, since a significant role is proposed for the sympathetics, a series of animals will undergo denervation of the lung by autotransplantation. This eliminates much of the vasoconstrictor response for 3 months. At that time, when the response reappears, the animals will undergo sympathectomy and reassessment of the hypoxic response to see if the newly-appeared response has been eliminated. If it has, then histologic verification of sympathetic regrowth will be sought using H & E scan sections followed by silver stains for verification. If the new response is not sympathetic mediated, then the role of histamine and prostaglandin will be investigated in this newly-appeared response.